Dr. Viviane Labrie is an assistant professor in Van Andel Research Institute’s Center for Neurodegenerative Science. Her area of expertise is the role of epigenetics in neurodegenerative diseases, a fledging field known as neuroepigenetics. But what exactly does that mean? We’ll let Dr. Labrie explain.

First thing’s first—what do you study?

We try to understand the biological origin of Parkinson’s disease and Alzheimer’s disease by studying the layer that is overlaid on top of the DNA code, so to speak. This layer—called the epigenome—controls access to the DNA and the genes contained within the DNA. Overall, the epigenome plays a huge role in how those genes are expressed. It’s sort of acts like the gatekeeper to DNA—it opens and closes doors on DNA.

Why study the epigenome? What are you looking for?

The epigenome is very important to the way genes work—it determines how much, where and when genes will be expressed. Epigenetic control over genes allows cells in the body to have different functions and to change over time. Its role in the body is very diverse, and includes everything from responding to foods we eat, to making new memories, to growing older, and so on.

As with other cells, the epigenome is very important to the activity of brain cells and, we believe, to the onset of neurodegenerative diseases as well. We know that the epigenome in brain cells changes as we age. Most of these aging changes are normal, but in certain regions we think that there is an accumulation of epigenetic errors over time. Once there is critical mass of epigenetic abnormalities, it could lead to the onset of diseases such as Parkinson’s and Alzheimer’s. For some people, the risk of acquiring these epigenetic abnormalities with age is even greater due to environment, lifestyle and inherited factors.

In our research, we are tackling the question of “where in the DNA do these epigenetic abnormalities occur?” DNA is a very big beast so it’s important to narrow our search to specific, important regions for each disease. In our analysis of samples from Parkinson’s and Alzheimer’s disease patients, we look specifically in regions of the DNA that are highly important for gene expression. These important regions are often found far down the DNA strand from the gene itself. Genes actually are only found in a small portion of the DNA. It’s the other areas—which actually used to be thought of as “junk”—that act like an on and off switch or a volume dial for regulating gene expression.

Investigating what the epigenome looks like in these gene regulatory regions gives us important clues as to the molecular changes involved in Parkinson’s and Alzheimer’s disease. We also look at molecular pathways that can be used to develop new therapies for Parkinson’s and Alzheimer’s, hopefully making a positive impact on people with these diseases.

How do errors in the epigenome occur?

It’s probably a combination of things. If you inherit certain genetic or epigenetic characteristics you’re more likely to accumulate epigenetic changes because these inherited factors set the stage for abnormalities to occur. The other components are environment and lifestyle, which also can play an important role. The epigenome reacts to environmental triggers, which can redirect the course of the epigenome with age. Inherited and environmental signals affecting the epigenome can ultimately promote the build up of aberrant changes that we think leads to disease onset.

When we talk about aging and age-related diseases, in particular Parkinson’s and Alzheimer’s, we have to remember the epigenome doesn’t exist in isolation. There are multiple layers to the way genes are organized. Our foot in the door is epigenetics. In reality, the mechanisms that contribute to disease are more complex than a single epigenetic change. It’s a huge cluster of changes to regions affecting gene activity that are important for a particular disease. It’s really a perfect storm of circumstances.

Check back next week for part two!Dr. Labrie also recently stopped by the WGVU Morning Show with Shelley Irwin. Check out her interview here.

Glossary

Epigenetics: Epigenetics is the study of factors outside of the genetic code that affect how the code (called DNA) is expressed. All cells in the body contain an almost identical set of genes, which are specific stretches of DNA that act as a “recipe” for building an organism. The epigenome tells these genes when to switch on or off and to what extent, altering how genes are expressed and, ultimately, the physical traits that result from this expression.

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